Accurate Profiling and Quantification of tRNA Fragments from RNA-Seq Data: A Vade Mecum for MINTmap.

There is an increasing interest within the scientific community in identifying tRNA-derived fragments (tRFs) and elucidating the roles they play in the cell. Such endeavors can be greatly facilitated by mining the numerous datasets from many cellular contexts that exist publicly. However, the standard mapping tools cannot be used for the purpose. Several factors complicate this endeavor including: the presence of multiple identical or nearly identical isodecoders at various genomic locations; the presence of identical sequence segments that are shared by isodecoders of the same or even different anticodons; the existence of numerous partial tRNA sequences across the genome; the existence of hundreds of "lookalike" sequences that resemble true tRNAs; and others. This is generating a need for specialized tools that can mine deep sequencing data to identify and quantify tRFs. We discuss the various complicating factors and their ramifications, and how to use and run MINTmap, a tool that addresses these considerations.

[1]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[2]  Lucian Ilie,et al.  SHRiMP2: Sensitive yet Practical Short Read Mapping , 2011, Bioinform..

[3]  Youri Hoogstrate,et al.  A comprehensive repertoire of tRNA-derived fragments in prostate cancer , 2016, Oncotarget.

[4]  A. Hopper,et al.  Multiple Layers of Stress-Induced Regulation in tRNA Biology , 2016, Life.

[5]  Jie Wu,et al.  tRF2Cancer: A web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers , 2016, Nucleic Acids Res..

[6]  Ilka U. Heinemann,et al.  3′–5′ tRNAHis guanylyltransferase in bacteria , 2010, FEBS letters.

[7]  O. Kohany,et al.  Repbase Update, a database of repetitive elements in eukaryotic genomes , 2015, Mobile DNA.

[8]  Patricia P. Chan,et al.  GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes , 2015, Nucleic Acids Res..

[9]  Peter F. Stadler,et al.  ViennaRNA Package 2.0 , 2011, Algorithms for Molecular Biology.

[10]  Isidore Rigoutsos,et al.  Consequential considerations when mapping tRNA fragments , 2016, BMC Bioinformatics.

[11]  Renato Vicentini,et al.  Genome-wide identification and characterization of tRNA-derived RNA fragments in land plants , 2016, Plant Molecular Biology.

[12]  Lisa Fish,et al.  Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement , 2015, Cell.

[13]  Isidore Rigoutsos,et al.  MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments , 2016, Bioinform..

[14]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Marcel Martin Cutadapt removes adapter sequences from high-throughput sequencing reads , 2011 .

[16]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[17]  J. Jackman,et al.  Life without post-transcriptional addition of G−1: two alternatives for tRNAHis identity in Eukarya , 2015, RNA.

[18]  Phillipe Loher,et al.  Nuclear and mitochondrial tRNA-lookalikes in the human genome , 2014, Front. Genet..

[19]  G. Meister,et al.  From tRNA to miRNA: RNA‐folding contributes to correct entry into noncoding RNA pathways , 2016, FEBS letters.

[20]  Patricia P. Chan,et al.  GtRNAdb: a database of transfer RNA genes detected in genomic sequence , 2008, Nucleic Acids Res..

[21]  Pankaj Kumar,et al.  tRFdb: a database for transfer RNA fragments , 2014, Nucleic Acids Res..

[22]  Ya-Ming Hou,et al.  CCA addition to tRNA: Implications for tRNA quality control , 2010, IUBMB life.

[23]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[24]  A. Hopper,et al.  tRNA biology charges to the front. , 2010, Genes & development.

[25]  Pavel Ivanov,et al.  tRNA fragments in human health and disease , 2014, FEBS letters.

[26]  Megumi Shigematsu,et al.  tRNA-Derived Short Non-coding RNA as Interacting Partners of Argonaute Proteins , 2015, Gene regulation and systems biology.

[27]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[28]  David J. States,et al.  QGB: Combined Use of Sequence Similarity and Codon Bias for Coding Region Identification , 1994, J. Comput. Biol..

[29]  S. Nelson,et al.  BFAST: An Alignment Tool for Large Scale Genome Resequencing , 2009, PloS one.

[30]  Leander Wyss,et al.  A tRNA-derived fragment competes with mRNA for ribosome binding and regulates translation during stress , 2016, RNA biology.

[31]  C. Mayr,et al.  Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells , 2009, Cell.

[32]  Ilka U. Heinemann,et al.  tRNAHis-guanylyltransferase establishes tRNAHis identity , 2011, Nucleic acids research.

[33]  Giovanni Nigita,et al.  Noncoding RNA: Current Deep Sequencing Data Analysis Approaches and Challenges , 2016, Human mutation.

[34]  Yi Jing,et al.  Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies , 2015, Oncotarget.

[35]  A. Orioli tRNA biology in the omics era: Stress signalling dynamics and cancer progression , 2017, BioEssays : news and reviews in molecular, cellular and developmental biology.

[36]  S. Eddy,et al.  tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. , 1997, Nucleic acids research.

[37]  S. Grewal Why should cancer biologists care about tRNAs? tRNA synthesis, mRNA translation and the control of growth. , 2015, Biochimica et biophysica acta.

[38]  Phillipe Loher,et al.  MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data , 2017, Scientific Reports.